Effects of congenital hypothyroidism on microtubule-associated protein-2 expression in the cerebellum of the rat.
In view of the defective neurotubule assembly observed in congenital hypothyroidism and the striking morphological abnormalities of the cerebellum in this condition, we have investigated the expression of microtubule-associated protein-2 (MAP2) in the cerebellum of rats with congenital hypothyroidism. Analysis included the measurement of immunoreactive MAP2 and its mRNA. In addition, the intracellular distribution of MAP2 was studied by immunostaining of the appropriate histological preparations. The results showed that the developmental increase in MAP2 is delayed in congenital hypothyroidism, but eventually the concentration of this protein reached normal levels in animals with this condition, even if untreated. These abnormalities in the immunoreactive protein are not paralleled by abnormalities in the abundance of MAP2 mRNA, which was not affected by the thyroid status of the animals. In spite of the normalization of the content of the protein, the distribution of MAP2 in the Purkinje cells of hypothyroid rats remained abnormal. Whereas in euthyroid rats the protein rapidly migrated into the dendrites, in the Purkinje cells of hypothyroid pups, MAP2 remained largely confined to the body and the most proximal part of the dendrites. These results suggest that thyroid hormone affects the expression of MAP2 at translation or posttranslational levels. The abnormality in distribution may result from some posttranslational abnormality of the protein itself or some underlying defect in the function of the neurons. These observations are probably relevant to the abnormalities in cerebellar function seen in animals and humans with untreated congenital hypothyroidism.
Silva
J E
JE
Thyroid Unit, Brigham and Women's Hospital, Boston, Massachusetts.
Rudas
P
P
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D003409:Congenital Hypothyroidism; D003600:Cytosol / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D015870:Gene Expression; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism; D007118:Immunoassay; D008713:Methimazole; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D008713:Methimazole